Introduction In order to fully utilize pharmacogenomic (PGx) testing for precision medicine, PGx assays must be comprehensive, scalable, and include robust coverage of difficult-to-sequence and difficult-to-map regions that are found in many clinically actionable PGx loci. Legacy low-cost technologies for PGx testing include targeted genotyping arrays, PCR-based assays, MLPA, and short-read sequencing; however, their limitations include biases towards known variants and/or populations, and can result in data that are incomplete or difficult to phase, potentially affecting phenotype prediction and subsequent clinical utility. Long-read PacBio HiFi sequencing allows for high accuracy and comprehensive variant calling, provides direct phasing (critical for unambiguous star (*) allele assignment), and is ancestry-agnostic. With targeted resequencing approaches, HiFi sequencing is also cost-efficient and high-throughput, allowing for scalable application to precision medicine research programs. Methods We designed an innovative 50-gene PGx panel for long-read HiFi sequencing that includes all 20 current genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, as well as FDA PGx genes and genes of interest to the PGx research community. The 2 Mb hybrid capture was designed by Twist Bioscience and samples were prepared following Twist Long Read Library Preparation and Standard Hyb v2 Enrichment Protocol optimized for long-read sequencing. Thirty-nine genes on the panel have full-gene coverage to enable complete phasing, and full-length mitochondrial DNA coverage is also included for quantitative interrogation of heteroplasmy. To assess the performance of the panel, we leveraged Genetic Testing Reference Material (GeT-RM) samples at a throughput of 24 samples per SMRT Cell 8M on a PacBio Sequel IIe system. Results For the 24 GeT-RM samples, samples had an average of 150k HiFi reads, with a mean read length of 5.3 kb. Mean target coverage was 190x across all target loci, with 96% of target regions exceeding 20x coverage, and 93% exceeding 30x. For star (*) allele assignments, multiple tools were compared, showing concordance and high accuracy of variant calls using a standard PacBio WGS pipeline. Conclusion Overall, the data demonstrate a scalable and cost-efficient long-read hybrid capture method for unbiased coverage and high accuracy of detecting PGx loci for both research and future implementation applications.